In people with HIV and plasma HIV RNA below the limit-of-quantification, discordant shedding of HIV RNA and DNA sequences from the genital tract was inferred to be from the proliferation of infected cells with virion production. This according to data published in The Journal of Infectious Diseases.
Discordant shedding is defined as episodic detection of HIV RNA in the genital tract but not in the plasma in patients with antiretroviral therapy (ART)-associated viral suppression. To evaluate whether discordant shedding is due to expression of virions from clones of infected cells, an investigation into this shedding of HIV RNA was conducted by following antiretroviral treatment (ART) naïve Peruvians for 2 years after from the moment they began treatment. Single HIV env and pol genomes were amplified from samples of discordant shedding and antiretroviral and cytokines/chemokines concentrations were compared at discordant shedding and control points.
A total of 82 participants had ART-suppression. Shedding was detected in 29% including, 13 of 253 (5%) cervicovaginal lavages, 20 of 322 (6%) seminal plasmas and 6 of 85 (7%) rectal secretions. The HIV RNA in shedding specimens was near the limit-of-quantification and not reproducible in repeated assays. In 6 of the 13 positive cervicovaginal lavages, HIV DNA was detected at low levels. Following a DNase treatment, 5 of 39 discordant shedding specimens yielded HIV sequences, all without increasing genetic distances. Similar plasma antiretroviral levels were found in women with and without shedding and discordant shedding in 1 woman was associated with inflammation.
Investigators noted that quantification of HIV RNA in genital tract specimens without prior DNase treatment precluded accurate estimates of the true prevalence of shedding RNA and was a limitation of this and likely other studies. Further limitations included a quarterly sampling regimen, that the majority of males refused to provide rectal samples and often only able to provide limited semen volumes.
According to investigators, “multiple findings from our study contribute data that refute the hypothesis that HIV replication causes [discordant shedding] and support the hypothesis that [discordant shedding] is the result of HIV-infected cell proliferation with viral RNA transcription leading to the production of virions.” Furthermore, the data suggested that discordant shedding poses a negligible, if any, risk of transmission and therefore does not counter the axiom, undetectable plasma equals untransmittable.
Bull M, Mitchell C, Soria J et al. Genital shedding of human immunodeficiency virus type-1 (HIV) when antiretroviral therapy (ART) suppresses HIV replication in the plasma [published online April 10 2020]. J Infect Dis. doi:10.1093/infdis/jiaa169